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Open Access Green as soon as Postprint is submitted to ZB.
SQSTM1/p62 variants in 486 patients with familial ALS from Germany and Sweden.
Neurobiol. Aging 87, 139.e9-139.e15 (2020)
Several studies reported amyotrophic lateral sclerosis (ALS)-linked mutations in TBK1, OPTN, VCP, UBQLN2, and SQSTM1 genes encoding proteins involved in autophagy. SQSTM1 was originally identified by a candidate gene approach because it encodes p62, a multifunctional protein involved in protein degradation both through proteasomal regulation and autophagy. Both p62 and optineurin (encoded by OPTN) are direct interaction partners and substrates of TBK1, and these 3 proteins form the core of a genetic and functional network that may connect autophagy with ALS. Considering the molecular and conceptual relevance of the TBK1/OPTN/SQSTM1 "triangle," we here performed a targeted screen for SQSTM1 variants in 486 patients with familial ALS from Germany and Sweden by analyzing whole-exome sequencing data. We report 9 novel and 5 previously reported rare variants in SQSTM1 and discuss the current evidence for SQSTM1 as a primary disease gene for ALS. We conclude that the evidence for causality remains vague for SQSTM1 and is weaker than for the other autophagy genes, for example, TBK1 and OPTN. (C) 2019 Elsevier Inc. All rights reserved.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Motor Neuron Disease ; Als ; Sqstm1 ; P62; Amyotrophic-lateral-sclerosis; Frontotemporal Lobar Degeneration; Mutations; Genes; Tbk1
ISSN (print) / ISBN
0197-4580
e-ISSN
1558-1497
Journal
Neurobiology of Aging
Quellenangaben
Volume: 87,
Pages: 139.e9-139.e15
Publisher
Elsevier
Publishing Place
New York, NY [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Human Genetics (IHG)